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Title: Temperature-Induced Replacement of Phosphate Proton with Metal Ion Captured in Neutron Structures of A-DNA

Abstract

Nucleic acids can fold into well-defined 3D structures that help determine their function. Knowing precise nucleic acid structures can also be used for the design of nucleic acid-based therapeutics. However, locations of hydrogen atoms, which are key players of nucleic acid function, are normally not determined with X-ray crystallography. Accurate determination of hydrogen atom positions can provide indispensable information on protonation states, hydrogen bonding, and water architecture in nucleic acids. Here, we used neutron crystallography in combination with X-ray diffraction to obtain joint X-ray/neutron structures at both room and cryo temperatures of a self-complementary A-DNA oligonucleotide d[GTGG(CSe)CAC] 2 containing 2'-SeCH3 modification on Cyt5 (C Se) at pH 5.6. We directly observed protonation of a backbone phosphate oxygen of Ade7 at room temperature. The proton is replaced with hydrated Mg 2+ upon cooling the crystal to 100 K, indicating that metal binding is favored at low temperature, whereas proton binding is dominant at room temperature.

Authors:
 [1];  [2];  [3];  [4];  [5]; ORCiD logo [6]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Neutron Scattering Division, Neutron Sciences Directorate; Georgia State Univ., Atlanta, GA (United States). Dept. of Chemistry
  2. Inst. Laue–Langevin, Grenoble (France). Large Scale Structures Group
  3. Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Rutherford Appleton Lab., ISIS Neutron Source
  4. SeNA Research Inc., Atlanta, GA (United States)
  5. Georgia State Univ., Atlanta, GA (United States). Dept. of Chemistry
  6. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Neutron Scattering Division, Neutron Sciences Directorate
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1506774
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Accepted Manuscript
Journal Name:
Structure
Additional Journal Information:
Journal Volume: 26; Journal Issue: 12; Journal ID: ISSN 0969-2126
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; A-form DNA; neutron crystallography; protonation; hydrogen bonding; metal binding; selenium modification

Citation Formats

Vandavasi, Venu Gopal, Blakeley, Matthew P., Keen, David A., Hu, Lillian R., Huang, Zhen, and Kovalevsky, Andrey. Temperature-Induced Replacement of Phosphate Proton with Metal Ion Captured in Neutron Structures of A-DNA. United States: N. p., 2018. Web. doi:10.1016/j.str.2018.08.001.
Vandavasi, Venu Gopal, Blakeley, Matthew P., Keen, David A., Hu, Lillian R., Huang, Zhen, & Kovalevsky, Andrey. Temperature-Induced Replacement of Phosphate Proton with Metal Ion Captured in Neutron Structures of A-DNA. United States. doi:10.1016/j.str.2018.08.001.
Vandavasi, Venu Gopal, Blakeley, Matthew P., Keen, David A., Hu, Lillian R., Huang, Zhen, and Kovalevsky, Andrey. Thu . "Temperature-Induced Replacement of Phosphate Proton with Metal Ion Captured in Neutron Structures of A-DNA". United States. doi:10.1016/j.str.2018.08.001. https://www.osti.gov/servlets/purl/1506774.
@article{osti_1506774,
title = {Temperature-Induced Replacement of Phosphate Proton with Metal Ion Captured in Neutron Structures of A-DNA},
author = {Vandavasi, Venu Gopal and Blakeley, Matthew P. and Keen, David A. and Hu, Lillian R. and Huang, Zhen and Kovalevsky, Andrey},
abstractNote = {Nucleic acids can fold into well-defined 3D structures that help determine their function. Knowing precise nucleic acid structures can also be used for the design of nucleic acid-based therapeutics. However, locations of hydrogen atoms, which are key players of nucleic acid function, are normally not determined with X-ray crystallography. Accurate determination of hydrogen atom positions can provide indispensable information on protonation states, hydrogen bonding, and water architecture in nucleic acids. Here, we used neutron crystallography in combination with X-ray diffraction to obtain joint X-ray/neutron structures at both room and cryo temperatures of a self-complementary A-DNA oligonucleotide d[GTGG(CSe)CAC]2 containing 2'-SeCH3 modification on Cyt5 (CSe) at pH 5.6. We directly observed protonation of a backbone phosphate oxygen of Ade7 at room temperature. The proton is replaced with hydrated Mg2+ upon cooling the crystal to 100 K, indicating that metal binding is favored at low temperature, whereas proton binding is dominant at room temperature.},
doi = {10.1016/j.str.2018.08.001},
journal = {Structure},
number = 12,
volume = 26,
place = {United States},
year = {2018},
month = {9}
}

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